Postdoctoral Research Assistant – DSTT MRC PPU

The role of TRAF6 in the immune system

TRAF6 is a RING-domain ubiquitin E3 ligase, which has an essential role in regulating many of the signalling pathway that control the development and functioning of the immune system. These include signalling pathways activated by components of microbial pathogens, such as Toll-Like Receptors and the recently discovered ALPKl-TIFA signalling pathway, and signalling pathways activated by cytokines of the lnterleukin-1 family and by TNF superfamily members. However, recent studies in our lab have unexpectedly revealed that, although the TRAF6 protein has an essential role in all these pathways, its E3 ligase activity is not essential (Strickson et al. (2017) Proc. Nat. Acad. Sci, USA 774, E23487- f3489; Petrioval et al (2022) PLoS ONE 17! : E026315 ; Snelling et al (2022) Biochem. J. 479, 2195-2216). The essential role of TRAF6 is therefore still unknown.

This project will focus on elucidation of the essential E3 ligase-independent roles ofTRAF6 in the innate immune system. The successful candidate will develop cell lines in which TRAF6 is replaced by E3-ligase inactive mutants and identify the proteins that form complexes with the E3 ligase-inactive TRAF6 when a variety of immune signalling pathways are activated. These proteins will be identified by a combination of immunoblotting and proteomics, but additional studies will be needed to distinguish proteins interacting directly with TRAF6 from those that interact with other TRAF6 binding proteins. Further research will depen! d on the outcome of these studies. The post would be suitable for scientists with

research experience in cell signalling, immunology and immunological techniques, immunoprecipitation and immunoblotting and proteomics.

Candidates must have a PhD in biochemistry, immunology or related discipline. The position will be an opportunity for candidates to broaden their skill-set by working in a multidisciplinary, well-funded lab using state-of-the-art technologies. Many of the scientists trained in this lab have subsequently become leaders in cell signalling with international reputations in the field.

Your priorities will include:

• Developing cell lines in which TRAF6 has been replaced by E3-ligase inactive mutants.
• Identifying proteins that form complexes with the E3 ligase-inactive mutants of TRAF6 when immune signalling pathways are activated.
• Preparation of results prior to the publication of papers
• Interacting with other lab members and collaborators
• Maintenance of meticulous lab records

Who we’re looking for:

Enthusiastic candidates must have completed a PhD in cell signalling related to immunology and have:

• A passion for research on cell signalling
• Experience in using immunological procedures.
• Experience in immunoprecipitation, immunoblotting and proteomics.

For further information about this position please contact Philip Cohen (p.cohen@dundee.ac.uk).To find out more about the MRC Protein Phosphorylation and ubiquitylation unit please visit www.ppu.mrc.ac.uk.

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